Alanine racemase (Mycobacterium tuberculosis) (Alr)

Alanine racemase (Alr) is a pyridoxal 5'-phosphate (PLP)-dependent enzyme essential for the growth and survival of Mycobacterium tuberculosis (UniProt: P9WIP9). It catalyzes the reversible racemization of L-alanine to D-alanine, a critical building block for the synthesis of the bacterial peptidoglycan cell wall (PubMed: 22411031). Because D-alanine is unique to bacteria and not synthesized by humans, alanine racemase represents a highly specific target for antitubercular drug development (PubMed: 25613164). The enzyme is primarily targeted by the second-line antibiotic D-cycloserine, which acts as a structural analog of D-alanine. Inhibition of this pathway leads to weakened cell walls and eventual bacterial lysis. Despite its efficacy, the use of drugs targeting this enzyme is often restricted to drug-resistant cases due to significant neurotoxic side effects resulting from cross-reactivity with human receptors.

Other names

AlrAlrAL-alanine racemaseAlanine racemase, PLP-binding

Competitive inhibition of the alanine racemase enzyme, which prevents the conversion of L-alanine to D-alanine, thereby depleting the pool of D-alanine required for the synthesis of the D-alanyl-D-alanine dipeptide used in peptidoglycan cross-linking (PubMed: 22411031).